It is proposed to continue studies in animals concerned with cerebral metabolism (CMR) and cerebral flow (CBF) with particular emphasis on the impact of anesthetic agents and techniques on ischemic brain. CBF will be measured by a direct venous ouflow method and CMRO2 and CMRglucose will be calculated from simultaneous measurements of CBF and arterial-sagittal sinus blood content differences. The cerebral energy state will be evaluated by measuring cerebral tissue levels of phosphocreatine, ATP, ADP, AMP, lactate, and pyruvate. A major thrust of this proposal is to examine the nature of barbiturate protection in animal models of cerebral ischemia. A dog model of global cerebral ischemia will be studied using a 10 minute ischemic period. This results in permanent severe neurologic damage unless pre-treated with pentobarbital (30 mg/kg) in which case neurologic damage is minimal or absent. Post-ischemic studies comparing CBF, CMRO2, CMRglucose, ICP, and the cerebral energy state in treated and untreated dogs will be carried out over a 24 hour period (the time required for recovery of treated dogs) and apparent barbiturate protective effects will be identified. The mechanism of barbiturate protection will be further evaluated in both this dog model and in an hypoxic mouse model. Non-anesthetic barbiturate isomers will be studied to determine if any protection results as would be expected if free radical scavenging or antioxidant effects are the basis for protection rather than metabolic depression. The effect of barbiturate tolerance on the protective effect will also be evaluated in these models. Barbiturate protection will also be compared to hypothermia protection in these two models in which CMRO2 is equally reduced by either barbiturates or hypothermia. In man a controlled study in patients undergoing cardiopulmonary bypass will be done to determine whether intraoperative thiopental reduces the incidence of postoperative neurologic deficits.